1. Field of the Invention
The present invention relates to neurotrophic and/or neurogenic peptides and their use for treating traumatic brain injuries.
2. Description of the Related Art
Traumatic Brain Injury (TBI) is the leading cause of death and disability in children and adults from ages 1 to 44 with an annual incidence of 1.7 million in the US, causing enormous economic burden and no proven therapy to improve long-term outcomes. Owing to the inherent vulnerability of hippocampus to trauma, cognitive impairment is widely accepted as the most devastating deficit in long-term survivors of TBI. In fact, hippocampal neuronal loss accompanies >80% of fatal TBI and apoptotic events in the hippocampus can be observed up to 12 months following TBI.
Observations from experimental models of TBI indicate enhanced stem cell proliferation in the hippocampal dentate gyrus (DG) following TBI and is widely considered an endogenous repair mechanism to counter cognitive decline after brain trauma. The biological drive behind increased stem cell proliferation in the hippocampus is based, in part, on neurotrophic factor dynamics within the local microenvironment. Consequently, increasing adult hippocampal neurogenesis and stimulating neuronal plasticity pharmacologically is considered a very useful strategy towards inhibiting cognitive decline following TBI.
Supplementing the hippocampus with neurotrophic factors that drive stem cells towards differentiation and sustain local microenvironment is a powerful concept in neuropharma. Several studies have reported enhancement of neurogenesis in TBI models through neurotrophic factor supplementation such as S100B, erthyropoietin, EGF and FGF and superior performance in memory tasks. While the administration of neurotrophic factors has generated much excitement in the literature, invasive mode of delivery, adverse side effects and difficult pharmacokinetics have very much limited the clinical usefulness of this approach